Although close to 85% of residents in long-term care facilities (LTC) have osteoporosis and the risk of osteoporotic fractures is nearly 10 times that of community dwelling elderly, few are treated and studies are scarce. To address this knowledge gap, we were awarded an NIA R01 (AG052123) in April 2016 to examine the efficacy and safety of denosumab to improve or maintain bone mineral density in a 2-year, randomized, double-blind, calcium-vitamin D controlled trial among 212 institutionalized, frail men and women ?65 years who reside in LTC facilities. After our study was started, pivotal trial data suggested an increase in multiple vertebral fractures with discontinuation of denosumab. This prompted the FDA to urge alternative therapy post-denosumab. Based on NIH DSMB input, we have developed a time- sensitive action plan. All participants would be treated with the intravenous bisphosphonate, zoledronic acid (zol) following trial completion. We applied for an administrative supplement for the medication as an initial stop gap. This competitive revision extends the specific aims of the parent trial to allow us to determine if bone loss and fractures are prevented with this safety measure. It will provide the first data on bone turnover and vertebral microarchitecture with this strategy. At month 24, as a part of the parent study, bone mineral density (BMD), biochemical markers of bone turnover (BTM), vertebral fracture assessment (VFA) and trabecular bone score (TBS) will be assessed. Specific aims for the competing revision and study extension following denosumab discontinuation: Aim 1: To evaluate maintenance of BMD: We will administer IV zol at 9 months (based on BTM data) after denosumab and assess BMD at month 27 (zol given), 33 (6 months post zol) and 39 (12 months post zol). H1: Zol will prevent BMD loss at the spine and hip following denosumab discontinuation. Aim 2: To evaluate BTM: We will examine bone resorption (CTX) and formation (P1NP) markers at month 27 (zol administration), 33 (6 months post zol) and 39 (12 months post zol). H2: BTM will remain stable and near or below month 0 during this period. Aim 3 (exploratory): To evaluate vertebral fractures and trabecular microstructure. We will examine VFA and TBS at month 27 (zol given), 33 (6 months post zol), and 39 (12 months post zol). H3: During this period, multiple vertebral fracture rate will be no greater than that during the initial 6- and 12-month periods in the placebo arm of the parent study; TBS will be maintained ? month 24 level. The study includes a number of innovative features: 1) focus on the neglected LTC population of frail adults, 2) inclusion of men, and 3) assessment of BMD, BTM, TBS microstructure and VFA to help understand the pathophysiology. Furthermore, it provides a feasible safety program to prevent the unanticipated outcome of multiple vertebral fractures following discontinuation of denosumab.